OVERVIEW OF TISSUE NECROSIS:
DELAYED RADIATION TREATMENT DAMAGE

Cancer Treatment
How Does Radiation Work
Kinds of Radiation Damage

     CANCER TREATMENT

    Modern treatment of cancer often involves a combination or selection of therapies: surgery to remove diseased tissue, and chemotherapy and/or radiation to destroy cancer cells and hopefully prevent metastasis, the spreading of cancer to a different location in the body.

    Surgery alone is traumatic to the body, involving removal of the tumor, as well as damage to the tissue around it. The surgeon often has to cut through healthy tissue to reach the tumor. Even on the skin, enough healthy tissue around the cancerous site has to be removed to ensure that there are no cancerous cells left behind to cause the tumor to recur. Thus, Moh’s surgery, where thin layers of skin are repeatedly removed and biopsied until a layer is ‘clean’ is often used, especially when a skin cancer recurs—the surgeon did not ‘get it all’ the first time.

    The theory of chemotherapy is to provide a carefully calculated systemic poison to the patient. Cancer cells grow faster than normal cells—they are ‘greedy’ in their consumption of nutrients. Because of their accelerated metabolism, they grab and process the chemotherapy drugs more quickly than the rest of the body. This is why chemotherapy can be an effective way to scout out and destroy rogue cells in the body—it doesn’t matter where they are hiding, their ‘me first’ attitude puts them directly in the line of fire.

    Radiation enables the physician to treat ‘hard to reach’ parts of the body, or places where the damage of reaching the tumor might exceed the benefit of excising it. It kills cells outright, inflicting lethal damage to ensure later cell death, stop cell replication, or inhibit collagen formation. Since tumor dells are less capable of DNA repair than healthy cells, they die off more quickly.

    Radiation may be the primary treatment, or it can be part of a treatment program involving chemotherapy and/or surgery. Often, radiation is used to shrink tumor size to make surgery easier. At other times, it is used as a post-surgical treatment to finish destroying residual cancer at the primary site. Although physicians are careful to minimize damage to healthy tissue, it is often unavoidable.

    Tissue death is the direct result of exposure to radiation. When radiation doses are divided (fractionated) and administered over time, each dose damages cellular DNA. Part of the strategy is to selectively treat cancer cells, knowing there will invariably be some “overflow.” Whether damage is to healthy tissue or tumor, radiation results in swelling and blood flow restriction in the immediate area of treatment. If radioactive “seeds” are implanted, tumor shrinkage may result in a greater amount of tissue being exposed than originally planned. Close monitoring throughout radiation treatment is required to minimize damage to healthy tissues.

    Although the greatest risk for cancer patients is inadequate treatment, the limits of the human body to endure both the immediate acute and long term late effects of radiation often force the physician to restrict exposure. Acute complications, direct cellular DNA damage, and cell death, are self-limiting and seldom restrict the dosage limit of radiation treatment.

    For years, physicians could not find a relationship between early and late damage. Now, it is understood that biochemical substances, including fibrogenic cytokines (which generate inflammation and the formation of scar tissue), appear early on. Elevation of these cytokine levels correlates with subsequent damage or the depression of other protective cytokines—either way, this early marker may predict a higher risk for late radiation damage. Instead of waiting to see whether or not the damage occurs, and its severity, physicians can now more effectively predict whether late radiation damage is a concern.

    Knowing the potential for late radiation damage is more significant if there is an effective prophylactic treatment that can be used in the latent period before injury becomes evident.

To date, the most successful treatment for this radiation injury is Hyperbaric Oxygen Therapy. HBOT increases the formation of new blood vessels into radiation damaged tissue and reduces the formation of thickened scar tissue (fibrosis).

     HOW DOES RADIATION WORK?

    When exposed to radiation, three cellular chemical changes occur:
        • the cellular protein structure is damaged, leading to cell death,
        • lipid peroxidation damages cell walls and energy storage,
        • and DNA damage.

    Cellular DNA is the critical target—the cell being most sensitive to radiation damage just before mitosis (where it grows by splitting into two cells). The faster cells are dividing (characteristic of cancer), the more sensitive they are to radiation damage. Cellular specialization decreases sensitivity; i.e., undifferentiated stem cells would be more susceptible to damage than cells of a specific organ.

    The difficulty has always been to deliver sufficient radiation treatment to kill cancerous tissue—with the long-term radiation damage unknown at the time of treatment. An effective radiation dosage may completely destroy the tumor—it is not unknown for the patient to die five years later from the vascular (blood vessel) and stromal (tissue supporting an organ) damage caused by the radiation. Yet, if treatment is not sufficient, remaining cancer cells can proliferate, causing recurring tumors and ultimate patient death.

    Treatment limitation becomes a matter of “best practices,” determining the most effective dosage, knowing that different organ systems have different tolerances to radiation, and understanding that long-term damage begins at the initiation of radiation treatment.

    Connective tissue, including the lining of the blood vessels, is less sensitive that cells in the process of dividing, but more sensitive than those which have completed the process. Damage to the blood vessels—swelling, degeneration, and vessel obliteration—may be a cause of delayed tissue death from radiation (necrosis) and probably accounts for the poor tissue healing observed when subsequent surgery is required.

     WHAT KINDS OF DAMAGE CAN RADIATION CAUSE?

    All radiation damage is not immediately apparent. Symptoms worsen over a long period of time, but damage begins when treatment starts. When damaged cells fail to reproduce and a restricted blood supply limits the ability of otherwise normal cells to grow and divide, the supportive collagen is lost, and tissue thickens and becomes stiff (fibrosis).

    Much tissue damage seems to originate in the destruction of the blood vessels serving the tissues, with the degree of premature aging, scarring, and ateriosclerosis within the vessels dependent on the type of radiation, exposure location and quantity, and individual patient factors.

    Helbach (1988) identified four types of damage resulting from radiation treatment:
        1) The acute period—the first 6 months. Organ damage accumulates, often with symptoms.
        2) The subacute period—the second 6 months. The body recovers from the acute period, but permanent tissue damage not only persists, it becomes worse.
        3) The chronic period—the second to fifth year. Residual damage continues to worsen. Capillaries and small blood vessels deteriorate causing a reduction in the delivery of oxygen to the body, damage to organ function, and reduced infection resistance.
        4) The late clinical period—after the fifth post-radiation year. Chronic period damage continues, along with premature aging and the development of new radiation-induced cancers (as opposed to recurrence of the original cancer).

The death of tissue (necrosis) during this period of time results from the radiation treatment years before.Thus, years after the cancer has been cured, radiation necrosis can be debilitating and cause death.

Late radiation damage begins at the initiation of treatment. Early acute damage is the result of cellular DNA and mucosal injury. Late radiation damage is primarily to the blood vessels and non-cancerous tissue around the tumor--it is the latter which limits radiation treatment. It is also this delayed radiation damage that HBOT has shown its effectiveness in treating.

    Blood vessels are not the only part of the body damaged by radiation. The skin, underlying soft tissues, and mucosal lining of the digestive and genitourinary tracts, may all suffer. Initially, the skin may become dry and itchy, red, peeling, weepy, and tender. Later, the skin may darken and atrophy (shrink) in affected areas, and become more prone to develop hard-to-heal ulcers in response to minor injuries.

    The consequences of radiation treatment often include fibrosis (the formation of scar tissue), and endarteritis (arterial inflammation and obliteration). These can result in reduced tissue oxygenation and necrosis (tissue death) years after the initial injury. Blood flow impairment is the reason why tissue dies even where there is no infection.

Hyperbaric oxygen treatment has been used to minimize and reverse blood vessel and supportive tissue damage by reducing swelling and scar tissue formation and encouraging the body to develop new capillaries into the radiated tissues. When proper levels of oxygen and nutrients are delivered, tissues heal more effectively, and necrosis can be avoided.

In the past, hyperbaric oxygen has been very successful in the treatment of delayed radiation-induced soft tissue and bony necrosis (tissue death). Although it seems least successful in the treatment of neurologic (central nervous system injuries), other treatments are also ineffective. The application which has had the earliest and most extensive study is for mandibular osteonecrosis, the death of jawbone tissue subsequent to irradiation and/or tooth extraction.

©2008 Florida Oxygen